REF MISC
CASR Gene, Full Gene Analysis
Performing Lab:
Referral Laboratory
Container Type:
Whole blood: Lavender-top (EDTA) tube; extracted DNA: sterile screw-capped vial
Specimen Type:
Whole blood or extracted DNA
Preferred Volume:
4 mL whole blood or 200 ng of DNA
Alternate Specimens:
oral swab: OCD-100 DNA Genotek device only -- This swab/kit is not stocked at Saint Luke's Regional Laboratories
Minimum Volume:
1 mL whole blood or 100 ng of DNA
Specimen Processing:
Blood: ship ASAP, but stable up to 5 days post-collection at room temperature. Do not freeze. ; DNA: ship at room temperature after extraction.
Store and Transport:
Room temperature
Stability:
Room temperature - Blood: 5 days
Refrigerated - Blood: 5 days
Do NOT Freeze.
Unacceptable Condition:
Frozen blood EDTA tube, Insufficient swab cell collection or incorrect oral swab device use; Extracted DNA A260:A280 ratio outside of 1.8 - 2.0 range.
CPT Codes:
81405
Method:
Nuclear Gene Single Nucleotide Variant and Small Indel Sequencing Assessment: Genomic regions of interest are selected using a custom capture reagent for target enrichment (Twist Bioscience) and sequenced via the Illumina® Novaseq 6000 next generation sequencing platform. Sequencing reads are aligned with the human genome reference GRCh37/hg19 build. Regions of interest include all exons and intron/exon junctions (+/-20 nucleotides) for each gene analyzed. A minimum of 99% of bases in targeted regions are covered at >15X. Analytical sensitivity is estimated to be >99% for single nucleotide variants, >97% for insertions/deletions less than six base pairs, and >95% for insertions/deletions between six and 15 base pairs. Uncovered regions with known pathogenic variants are sequenced in a targeted manner (List based on ClinVar Database: July 22, 2019, release). Nuclear Gene Copy Number Variant Assessment: Next Generation Sequencing data used to call SNPs and small indels are assessed with Illumina’s DRAGEN (Dynamic Read Analysis for GENomics) Bio-IT Platform. Genes listed in ClinVar with intragenic pathogenic deletions are padded with additional intronic probes to allow single exon resolution CNV detection (List based on ClinVar Deletion Database: January 2019 release). For other genes, large deletions (>10 exons) can be detected. The resolution of this analysis can vary depending on region-specific features. Analytical sensitivity is estimated to be >95%
Clinical Significance:
Diagnostic testing. CASR gene sequencing may be useful in the diagnostic workup of familial hypocalciuric hypercalcemia (FHH), autosomal dominant hypocalcemia, neonatal severe primary hyperparathyroidism (NSPHT), autosomal dominant hypoparathyroidism (ADH), Bartter syndrome, or kidney stones.